Chain transfer agents for raft polymerization in aqueous media

ABSTRACT

Polymers and copolymers synthesized by means that yield a narrow range of molecular weights can have different properties than polymers synthesized by conventional means. In order to obtain such polymers, however, polymerization must be controlled. One type of controlled polymerization is the reversible addition-fragmentation chain transfer (RAFT) process, which has characteristics of a living polymerization. The present invention discloses a group of dithioesters and trithioesters suitable as chain transfer agents for RAFT polymerization. The present invention also discloses RAFT polymerizations conducted in aqueous media.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.11/057,760 filed Feb. 14. 2005 now U.S. Pat. 7,179,872, which is adivisional of U.S. application Ser. No. 10/337,225 filed Jan. 6, 2003,now U.S. Pat. No. 6,855,840 which is a continuation-in-part of U.S.application No. 10/073,820, filed Feb. 11, 2002 now abandoned, theentire teachings which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

In a polymer or copolymer synthesis, achieving a product with a desiredmolecular weight and a narrow weight distribution, or polydispersity,requires a controlled process. Polymers with a narrow molecular weightdistribution can exhibit substantially different behavior and propertiesthan polymers prepared by conventional means. Living polymerizationsprovide the maximum degree of control for the synthesis of polymers withpredictable well-defined structures. The characteristics of a livingpolymerization include: polymerization proceeding until all monomer isconsumed, number average molecular weight as a linear function ofconversion, molecular weight control by the stoichiometry of thereaction, and block copolymer preparation by sequential monomeraddition.

It has been stated that living polymerization to give polymers of lowmolecular weight distribution requires the absence of chain transfer andtermination reactions. In a living polymerization, the only “allowed”elementary reactions are initiation and propagation, which take placeuniformly with respect to all growing polymer chains. However, it hasalso been shown that if the chain transfer process is reversible,polymerization can still possess most of the characteristics of livingpolymerization.

It has been found that the reversible addition-fragmentation chaintransfer (RAFT) process suppresses termination reactions through theaddition of a suitable thiocarbonylthio compound, also known as adithioester, to an otherwise conventional free radical polymerization.Control in such a RAFT process is thought to be achieved through adegenerative chain transfer mechanism in which a propagating radicalreacts with the thiocarbonylthio compound to produce an intermediateradical species. This process decreases the number of free radicalsavailable for termination reactions that require two free radicals.

Although RAFT polymerizations have been demonstrated to work under avariety of conditions, further research is required to demonstrate theeffectiveness of RAFT polymerizations in aqueous solvent systems.Specifically, there is a need to develop dithioester chain transferagents that are both soluble and stable in water. Also, there is a needto develop dithioesters that are tailored to the monomer beingpolymerized.

SUMMARY OF THE INVENTION

It has been found that a large group of compounds comprising adithioester moiety act as excellent chain transfer agents in the RAFTprocess of producing polymers. It has further been found that many ofthese dithioesters and trithioesters, under the proper conditions, arestable towards hydrolysis in water and can be used in this medium tocontrol free radical polymerizations. In addition, it has been foundthat a dithioester, particularly a water-soluble dithioester, withelectronic and/or structural similarities to the monomer beingpolymerized is particularly desirable. These dithioesters are able topolymerize a wide range of related monomers in water to yieldwater-soluble polymers of controlled molecular weight, molecular weightdistribution, and tailored architectures.

In one embodiment, the present invention is a group of dithioesters andtrithioesters represented by the structural formula:

where Z in the dithioesters comprises an alkoxy group, a grouprepresented by the structural formula:

or one or more aromatic or heteroaromatic groups optionally substitutedby one or more hydrophilic functional groups with optionally an ether oralkylene linkage between said aromatic- or heteroaromatic-containinggroup and the dithioester moiety; and R comprises a group represented bythe structural formula:

where Ar is an aromatic or heteroaromatic group; L is a bond, an C1-C20azaalkylene group, or a C1-C20 straight-chained or branched alkylenegroup; R₁ and R₂ are each independently hydrogen, a C1-C10 alkyl group,or a cyano group; R₃ and R₄ are each independently hydrogen or a C1-C10alkyl group when Y is N or C, and are each lone electron pairs when Y isO; R₅ is a bond or a branched or straight-chained C1-C10 alkylene group;R₆ is hydrogen or a C1-C10 alkyl group; W is selected from the groupconsisting of —H, —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂, —NR′H, —NR′₃⁺X⁻, —PO₄ ^(−M) ⁺, —OH, —(—OCH₂CH₂—)_(x)R′, —(—CH₂CH₂O—)_(x)R′, —CONH₂,—CONHR′, —CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,—NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺,—N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺, —SCN, naphthyl, and dansyl; M⁺ is ammonia, anammonium ion, an alkali metal ion, an alkaline earth metal ion, orhydronium; R′ is independently hydrogen or an alkyl group; x is aninteger from 1 to about 20; X⁻ is a halide, sulfate, phosphate,carboxylate, or sulfonate; and Y is selected from the group consistingof N, O, and C.

In a preferred embodiment, R₁ and R₂ are each independently hydrogen ora methyl group.

In another embodiment, the present invention is a method of preparing apolymer or copolymer, comprising reacting a polymerizable monomer orco-monomer, a dithioester or trithioester of the present invention, andfree radicals produced by a free radical source in a solvent.Preferably, the solvent is water and optionally a water-miscible organicsolvent such as dimethylformamide. Even more preferably, the solvent iswater. When polymerizing monomer or comonomers having an acrylamidemoiety, the pH of the solvent (e.g., water) is advantageously acidic,for example, where the pH is greater than about 2 and less than aboutor, in some instances, greater than about 4 and less than about 6 or, inmore particular instances, greater than about 4.5 and less than about5.5.

The present invention has many advantages. Dithioesters andtrithioesters of the present invention are capable of controlling apolymerization, such that the molecular weight of the polymers can beregulated and the molecular weight distribution is within a narrowrange. Dithioesters of the present invention are also largely soluble inwater and undergo slow hydrolysis. When controlled (RAFT)polymerizations are carried out with these dithioesters, thepolymerization can be conducted in water, largely or entirelyeliminating the need for and cost of organic solvents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A-FIG. 1C shows (A) size exclusion chromatograms (SEC) for PDMAwith chain transfer agent (CTA)N,N-dimethyl-s-thiobenzoylthiopropionamide (1c) (target MW=40,000) ind₆-benzene at 60° C. using a CTA/initiator (D ratio of 5/1,[monomer]=1.95 M, [CTA]=4.27×10⁻³, [I]=8.46×10⁻⁴, (B) plot of in(M_(o)/M_(t)) as a function of polymerization time, and (C) evolution ofnumber average number weight and polydispersity (M_(w)/M_(n)) withconversion.

FIG. 2 shows plots of In (MW_(o)/MW_(t)) versus time forN,N-dimethylacrylamide (DMA) polymerizations in an NMR spectrometer inC₆D₆ (60° C.) using CTAs 1a-1d.

FIG. 3A-FIG. 3D shows SEC traces for DMA polymerizations using CTA/I of5/1 for CTA 1a-1d in C₆D₆ (60° C.) at extended polymerization times.

FIG. 4 shows aqueous SEC for poly(DMA) synthesized in the presence ofsodium 4-cyamopentanoic acid dithiobenzoate (CTPNa) in water at 80° C.The insert shows poly(DMA) synthesized under identical conditions in thepresence of TBP.

FIG. 5 shows kinetic plots for the polymerization of DMA in the presenceof CTPNa at 60° C., 70° C., and 80° C. and in the presence of TBP at 80°C. for concentrations of 0.0 M, 0.9 M, 1.8 M, and 3.7 M DMF in H₂O.

FIG. 6 shows plots of molecular weight versus concentration forpoly(DMA) synthesized at 60° C., 70° C., and 80° C. in the presence ofCTPNa, at 80° C. in the presence ofN,N-dimethyl-s-thiobenzoylthiopropionamide (TBP), at 80° C. in 3.7 M DMFin H₂O in the presence of TBP.

FIG. 7 shows typical results for the polymerization of acrylamide in thepresence of a dithioester under ambient pH conditions. At 2 hours, nopolymer was observed; at 4 hours, all color bleached from the reactionmedium and the polymer had a mean molecular weight of 24,900 and apolydispersity index (PDI) of 1.09; at 8 hours, the polymer had a meanmolecular weight of 114,000 and a PDI of 1.87; at 12 hours, the polymerhad a mean molecular weight of 239,000 and a PDI of 2.98.

FIG. 8A shows ASEC chromatographs (RI traces) for the polymerization ofacrylamide in an acetic acid/sodium acetate buffer showing the evolutionof molecular weight with time.

FIG. 8B shows a first order rate plot for the polymerization ofacrylamide in an acetic acid/sodium acetate buffer.

FIG. 8C show the plot of degree of polymerization DP_(n) versusconversion for the polymerization of acrylamide in an acetic acid/sodiumacetate buffer.

FIG. 9 shows ASEC chromatographs (RI traces) for the polymerization ofacrylamide in an acetic acid/sodium acetate buffer using apolyacrylamide macro-CTA as the chain transfer agent and showing theevolution of molecular weight.

DETAILED DESCRIPTION OF THE INVENTION

A useful and efficient process for producing polymers and copolymersfrom monomers is the carrying out of a reversible addition-fragmentationchain transfer (RAFT) procedure with dithioesters or trithioesters aschain transfer agents (CTA's). The dithioester and trithioester chaintransfer agents of the present invention are particularly advantageous.They can be used to produce polymers with low polydispersities. Many ofthe dithioester CTA's of the present invention can be used to produce avariety of polymers by the RAFT procedure in aqueous media.

The dithioesters and trithioesters of the present invention can berepresented by the structural formula:

In this structural formula, Z comprises an alkoxy group, a grouprepresented by the structural formula:

or one or more aromatic or heteroaromatic groups optionally substitutedby one or more hydrophilic functional groups with optionally an ether oralkylene linkage between said aromatic- or heteroaromatic-containinggroup and the dithioester moiety. R comprises a group represented by thestructural formula:

where Ar is an aromatic or heteroaromatic group; L is a bond, an C1-C20azaalkylene group, or a C1-C20 straight-chained or branched alkylenegroup; R₁ and R₂ are each independently hydrogen, a C1-C10 alkyl group,or a cyano group; R₃ and R₄ are each independently hydrogen or a C1-C10alkyl group when Y is N or C, and are each lone electron pairs when Y isO; R₅ is a bond or a branched or straight-chained C1-C10 alkylene group;R₆ is hydrogen or a C1-C10 alkyl group; W is selected from the groupconsisting of —H, —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂, —NR′H, —NR′₃⁺X⁻, —PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)R′, —(—CH₂CH₂O—)_(x)R′, —CONH₂,—CONHR′, —CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,—NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺,and —N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺, naphthyl, and dansyl; M⁺ is ammonia, anammonium ion, an alkali metal ion, an alkaline earth metal ion, orhydronium; R′ is independently hydrogen or an alkyl group; x is aninteger from 1 to about 20; X⁻ is a halide, sulfate, phosphate,carboxylate, or sulfonate; and Y is selected from the group consistingof N, O, and C.

R and Z groups of the present invention are preferably substituted byone or more hydrophilic functional groups. These hydrophilic functionalgroups include SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂, —NR′H, —NR′₃ ⁺X⁻,—PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)H, —CONH₂, —CONHR′, —CONR′₂,—NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺, —NR′(CH₂)_(x)SO₃ ⁻M⁺,—N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺,or a combination thereof; and M⁺, R′, x, and X⁻ are as previouslydefined.

Preferred Z groups of the present invention comprise a phenyl, benzyl,pyrrole, indole, isoindole, or ethoxy group. Especially preferred Zgroups are represented by structural formulae:

Preferred R groups are represented by the structural formulae:

where m and n are each integers from 1 to about 10; R₇, R₈, R₉, R₁₀, andR₁₁ are each independently hydrogen or a C1-10 alkyl group; L, M⁺, R′,W, X⁻, x, and Y are as previously defined; and V is selected from thegroup consisting of C and N. Preferably, R₇ and R₈ are eachindependently hydrogen or a methyl group.

Especially preferred R groups of the present invention are representedby the structural formulae:

where M⁺, X⁻ and x are as previously defined.

Additional suitable R groups of the present invention are represented bythe structural formulae:

Preferred dithioesters of the present invention are represented by thestructural formulae:

where R is as previously defined.

Especially preferred dithioesters of the present invention arerepresented by the structural formulae:

In another preferred embodiment, the dithioester is represented by thestructural formula:

where:

-   -   j is an integer from 1 to about 12, preferably 1 to about 6,        more preferably 1 to 4, and even more about preferably 2;    -   k is an integer from 0 to 5, preferably 0 or 1, more preferably        0;    -   each R_(p) is the same or different and is selected from the        group consisting of —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂,        —NR′H, —NR′₃ ⁺X⁻, PO₄ ^(−M) ⁺, —OH, —(OCH₂CH₂)_(x)OH, —CONH₂,        —CONHR′, —CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,        —NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃        ⁻M⁺, —N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺ and —SCN;    -   W is selected from the group consisting of —SO₃ ⁻M⁺, —COOH,        —COO⁻M⁺, —PO₄ ⁻M⁺, —NR′₂, —NR′₃ ⁺X⁻, —NR′(CH₂)_(x)COO⁻M⁺,        —NR′(CH₂)_(x)OPO₃ ⁻M⁺, —NR′(CH₂)_(x)SO₃ ⁻M⁺,        —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺ and        —N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺; preferably —SO₃ ⁻M⁺;    -   M⁺ is ammonia, an ammonium ion, an alkali metal ion, an alkaline        earth metal ion, or hydronium, preferably an alkali metal ion        such as sodium;    -   R′ is independently hydrogen or an alkyl group    -   X⁻ is selected from the group consisting of halide, sulfate,        phosphate, carboxylate and sulfonate; and    -   x is an integer from 1 to about 20.

While not being bound by any one mechanism, RAFT polymerizations with asingly-functional chain transfer agent (CTA), such as a dithioester, arethought to occur by the mechanism illustrated in Scheme 1. Briefly, aninitiator produces a free radical, which subsequently reacts with apolymerizable monomer. The monomer radical reacts with other monomersand propagates to form a chain, P_(n)• which can react with a CTA. TheCTA can fragment, either forming R•, which will react with anothermonomer that will form a new chain, P_(m)•, or P_(n)•, which willcontinue to propagate. In theory, propagation of P_(m)• and P_(n)• willcontinue until no monomer is left and a termination step occurs. Afterthe first polymerization has finished, in particular circumstances, asecond monomer can be added to the system to form a block copolymer. Thepresent invention can also be used to synthesize multiblock, graft,star, gradient, and end-functional polymers.

Suitable polymerizable monomers and comonomers of the present inventioninclude methyl methacrylate, ethyl acrylate, propyl methacrylate (allisomers), butyl methacrylate (all isomers), 2-ethylhexyl methacrylate,isobornyl methacrylate, methacrylic acid, benzyl methacrylate, phenylmethacrylate, methacrylonitrile, alpha-methylstyrene, methyl acrylate,ethyl acrylate, propyl acrylate (all isomers), butyl acrylate (allisomers), 2-ethylhexyl acrylate, isobornyl acrylate, acrylic acid,benzyl acrylate, phenyl acrylate, acrylonitrile, styrene, acrylates andstyrenes selected from glycidyl methacrylate, 2-hydroxyethylmethacrylate, hydroxypropyl methacrylate (all isomers), hydroxybutylmethacrylate (all isomers), N,N-dimethylaminoethyl methacrylate,N,N-diethylaminoethyl methacrylate, triethyleneglycol methacrylate,itaconic anhydride, itaconic acid, glycidyl acrylate, 2-hydroxyethylacrylate, hydroxypropyl acrylate (all isomers), hydroxybutyl acrylate(all isomers), N,N-dimethylaminoethyl acrylate, N,N-diethylaminoethylacrylate, triethyleneglycol acrylate, methacrylamide,N-methylacrylamide, N,N-dimethylacrylamide, N-tert-butylmethacrylamide,N-n-butylmethacrylamide, N-methylolacrylamide, N-ethylolacrylamide,vinyl benzoic acid (all isomers), diethylaminostyrene (all isomers),alpha-methylvinyl benzoic acid (all isomers), diethylaminoalpha-methylstyrene (all isomers), p-vinylbenzenesulfonic acid,p-vinylbenzene sulfonic sodium salt, trimethoxysilylpropyl methacrylate,triethoxysilylpropyl methacrylate, tributoxysilylpropyl methacrylate,dimethoxymethylsilylpropyl methacrylate,diethoxymethylsilylpropylmethacrylate, dibutoxymethylsilylpropylmethacrylate, diisopropoxymethylsilylpropyl methacrylate,dimethoxysilylpropyl methacrylate, diethoxysilylpropyl methacrylate,dibutoxysilylpropyl methacrylate, diisopropoxysilylpropyl methacrylate,trimethoxysilylpropyl acrylate, triethoxysilylpropyl acrylate,tributoxysilylpropyl acrylate, dimethoxymethylsilylpropyl acrylate,diethoxymethylsilylpropyl acrylate, dibutoxymethylsilylpropyl acrylate,diisopropoxymethylsilylpropyl acrylate, dimethoxysilylpropyl acrylate,diethoxysilylpropyl acrylate, dibutoxysilylpropyl acrylate,diisopropoxysilylpropyl acrylate, vinyl acetate, vinyl butyrate, vinylbenzoate, vinyl chloride, vinyl fluoride, vinyl bromide, maleicanhydride, N-phenylmaleimide, N-butylmaleimide, N-vinylpyrrolidone,N-vinylcarbazole, butadiene, isoprene, chloroprene, ethylene, propylene,1,5-hexadienes, 1,4-hexadienes, 1,3-butadienes, and 1,4-pentadienes.

Additional suitable polymerizable monomers and comonomers includevinylalcohol, vinylamine, N-alkylvinylamine, allylamine,N-alkylallylamine, diallylamine, N-alkyldiallylamine, alkylenimine,acrylic acids, alkylacrylates, acrylamides, methacrylic acids,alkylmethacrylates, methacrylamides, N-alkylacrylamides,N-alkylmethacrylamides, styrene, vinylnaphthalene, vinyl pyridine,ethylvinylbenzene, aminostyrene, vinylbiphenyl, vinylanisole,vinylimidazolyl, vinylpyridinyl, dimethylaminomethylstyrene,trimethylammonium ethyl methacrylate, trimethylammonium ethyl acrylate,dimethylamino propylacrylamide, trimethylammonium ethylacrylate,trimethylammonium ethyl methacrylate, trimethylammonium propylacrylamide, dodecyl acrylate, octadecyl acrylate, and octadecylmethacrylate.

Preferred polymerizable monomers and comonomers includealkylacrylamides, methacrylamides, acrylamides, styrenes, allylamines,allylammonium, diallylamines, diallylammoniums, alkylacrylates,methacrylates, acrylates, n-vinyl formamide, vinyl ethers, vinylsulfonate, acrylic acid, sulfobetaines, carboxybetaines,phosphobetaines, and maleic anhydride.

Even more preferred polymerizable monomers and comonomers includealkylacrylates, methacrylates, acrylates, alkylacrylamides,methacrylamides, acrylamides, and styrenes.

Especially preferred monomers and comonomers include acrylamide,2-acrylamido-2-methylpropane sulfonate, 3-acrylamido-3-methylbutanoate,N,N-dimethylacrylamide, vinyl benzoic acid, vinylN,N,N-trimethylammoniomethylbenzene, vinylN,N-dimethylaminomethylbenzene and styrene sulfonate.

The source of free radicals can be any suitable method of generatingfree radicals such as thermally induced homolytic scission of a suitablecompound(s) (thermal initiators such as peroxides, peroxyesters, or azocompounds), the spontaneous generation from a monomer (e.g., styrene),redox initiating systems, photochemical initiating systems or highenergy radiation such as electron beam, X- or gamma-ray radiation. Theinitiating system is chosen such that under the reaction conditions,there is no substantial adverse interaction of the initiator, theinitiating conditions, or the initiating radicals with the transferagent under the conditions of the procedure. The initiator should alsohave the requisite solubility in the reaction medium or monomer mixture.

Thermal initiators are chosen to have an appropriate half-life at thetemperature of polymerization. These initiators can include one or moreof 2,2′-azobis(isobutyronitrile), 2,2′-azobis(2-cyano-2-butane),dimethyl 2,2′-azobisdimethylisobutyrate, 4,4′-azobis(4-cyanopentanoicacid), 1,1′-azobis(cyclohexanecabonitrile),2-(t-butylazo)-2-cyanopropane,2,2-azobis[2-methyl-N-(1,1)-bis(hydroxyethyl)]-propionamide,2,2′-azobis(N,N′-dimethyleneisobutyramidine) dihydrochloride,2,2′-azobis (N,N′-dimethyleneisobutyramine),2,2′-azobis(2-methyl-N-[1,1-bis(hydroxymethyl)-2-hydroxyethyl]propionamide,2,2′-azobis[2-methyl-N-(2-hydroxyethyl)propionamide],2,2′-azobis(isobutyramide)dihydrate,2,2′-azobis(2,2,4-trimethylpentane), 2,2′-azobis (2-methylpropane),t-butyl peroxyacetate, t-butyl peroxybenzoate, t-butyl peroxyoctoate,t-butyl peroxyneodecanoate, t-butylperoxy isobutyrate, t-amylperoxypivalate, t-butyl peroxypivalate, di-isopropyl peroxydicarbonate,dicyclohexyl peroxydicarbonate, dicumyl peroxide, dibenzoyl peroxide,dilauroyl peroxide, potassium peroxydisulfate, ammonium peroxydisulfate,di-t-butyl, hyponitrite, and dicumyl hyponitrite.

Photochemical initiator systems are chosen to have the requisitesolubility in the reaction medium or monomer mixture and have anappropriate quantum yield for radical production under the conditions ofthe polymerization. Examples include benzoin derivatives, benzophenone,acyl phosphine oxides, and photo-redox systems.

Redox initiator systems are chosen to have the requisite solubility inthe reaction medium or monomer mixture and have an appropriate rate ofradical production under the conditions of the polymerization; theseinitiating systems can include combinations of oxidants such aspotassium peroxydisulfate, hydrogen peroxide, t-butyl hydroperoxide andreductants such as iron(II), titanium(III), potassium thiosulfite, andpotassium bisulfite.

Other suitable initiating systems are described in recent texts. See,for example, Moad and Solomon, “The Chemistry of Free RadicalPolymerization,” Pergamon, London, 1995, pp. 53-95.

Polymerizations of the present invention can occur in any suitablesolvent or mixture thereof. Suitable solvents include water, alcohol(e.g., methanol, ethanol, n-propanol, isopropanol, butanol),tetrahydrofuran (THF) dimethyl sulfoxide (DMSO), dimethylformamide(DMF), acetone, acetonitrile, hexamethylphosphoramide, acetic acid,formic acid, hexane, cyclohexane, benzene, toluene, methylene chloride,ether (e.g., diethyl ether), chloroform, and ethyl acetate. Preferredsolvents include water, and mixtures of water and water-miscible organicsolvents such as DMF. Water is an especially preferred solvent.

In a preferred embodiment of the present invention, a polymer orcopolymer is prepared where the following are reacted together in asolvent or solvent mixture (e.g., water or a mixture of water anddimethylformamide): N,N-dimethylacrylamide,N,N-dimethyl-s-thiobenzoylthio-2-propionamide or sodiumthiobenzoylthio-s-4-cyano-4-pentainoate,and free radicals produced by afree radical source.

It desirable to choose reaction components (solvent, etc.), such thatthe components have a low transfer constant towards the propagatingradical. Chain transfer to these species will lead to the formation ofchains that do not contain an active dithioester group.

In addition to the choice of dithioester, monomer or comonomer, freeradical source, and solvent, the choice of polymerization conditions isalso important. The reaction temperature will influence the rate. Forexample, higher reaction temperatures will typically increase the rateof fragmentation. Conditions should be chosen such that the number ofchains formed from initiator-derived radicals is minimized to an extentconsistent with obtaining an acceptable rate of polymerization.Termination of polymerization by radical-radical reactions will lead tochains that contain no active group and therefore cannot be reactivated.The rate of radical-radical termination is proportional to the square ofthe radical concentration. Furthermore, in the synthesis of block, star,or branched polymers, chains formed from initiator-derived radicals willconstitute a linear homopolymer impurity in the final product. Thereaction conditions for these polymers therefore require careful choiceof initiator concentration and, where appropriate, the rate of initiatorfeed.

As a general guide in choosing conditions for the synthesis of narrowdispersity polymers, the concentration of initiator(s) and otherreaction conditions (solvent(s), temperature, pressure) should be chosensuch that the molecular weight of polymer formed in the absence of theCTA is at least twice that formed in its presence. In polymerizationswhere termination is solely by disproportionation, this equates tochoosing an initiator concentration such that the total moles ofinitiating radicals formed during the polymerization is less than 0.5times that of the total moles of CTA. More preferably, conditions shouldbe chosen such that the molecular weight of polymer formed in theabsence of the CTA is at least 5-fold that formed in its presence.

The polydispersity of polymers and copolymers synthesized by the methodof the present invention can be controlled by varying the ratio of thenumbers of molecules of CTA to initiator. A lower polydispersity isobtained when the ratio of CTA to initiator is increased. Conversely, ahigher polydispersity is obtained when the ratio of CTA to initiator isdecreased. Preferably, conditions are selected such that polymers andcopolymers have a polydispersity less than about 1.5, more preferablyless than about 1.3, even more preferably less than about 1.2, and yetmore preferably less than about 1.1. In conventional free radicalpolymerizations, polydispersities of the polymers formed are typicallyin the range of 1.6-2.0 for low conversions (<10%) and are substantiallygreater than this for higher conversions. For the polymerization ofmonomers or comonomers based on acrylamide (e.g., having an acrylamidemoiety), acceptable polydispersities have been obtained when the ratioof CTA (e.g., a dithioester or trithioester of the present invention) toinitiator (free radical source) is about 0.8 to about 1.6, aboutpreferably 0.9 to about 1.5, more preferably about 1.0 to about 1.4 orstill more preferably about 1.1 to about 1.3.

With these provisos, the polymerization process according to the presentinvention is performed under the conditions typical of conventionalfree-radical polymerization. Polymerizations employing the abovedescribed dithioesters are suitably carried out at temperatures in therange −20 to 200° C., preferably 20 to 150° C., more preferably 50 to120° C., or even more preferably 60 to 90° C. The pH of a polymerizationconducted in aqueous solution can also be varied. The pH is selected inpart so that the selected dithioester is stable and propagation of thepolymer occurs. Typically, the pH is from about 0 to about 9, preferablyfrom about 1 to about 7, more preferably from about 2 to about 6.5. ThepH can be adjusted following polymerization, particularly when thepolymer is a copolymer, such that one monomer of the copolymer ischarged and another monomer is uncharged or of opposite charge.

As discussed above, when the monomer or comonomer is acrylamide orcontains an acrylamide moiety, the polymerization is advantageouslycarried out in an acidic solution, such as a buffered aqueous solution.An acetate buffer, for example, has been found to work well. The pH ofsuch solutions typically is greater than about 1 and less than about 7,more typically greater than about 2 and less than about 7, still moretypically greater than about 4 and less than about 6 or, in certaininstances, greater than about 4.5 and less than about 5.5.

Aromatic groups of the dithioesters, as defined herein, includecarbocyclic aromatic groups such as phenyl, benzyl, 1-naphthyl,2-naphthyl, 1-anthracyl, 2-anthacyl, phenanthrenyl, pyrenyl, andbiphenyl. Heterocyclic aromatic groups include groups such asN-imidazolyl, 2-imidazole, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 2-pyridyl, 3-pyridyl,4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 2-pyranyl, 3-pyranyl, 3-pyrazolyl,4-pyrazolyl, 5-pyrazolyl, 2-pyrazinyl, 2-thiazole, 4-thiazole,5-thiazole, 2-oxazolyl, 4-oxazolyl and 5-oxazolyl.

Heteroaromatic groups also include fused polycyclic aromatic ringsystems in which a carbocyclic aromatic ring or heteroaryl ring is fusedto one or more other heteroaryl rings. Examples include 2-benzothienyl,3-benzothienyl, 2-benzofuranyl, 3-benzofuranyl, 1-indolyl, 2-indolyl,3-indolyl, 2-quinolinyl, 3-quinolinyl, 2-benzothiazole, 2-benzooxazole,2-benzimidazole, 2-quinolinyl, 3-quinolinyl, 1-isoquinolinyl,3-quinolinyl, 1-isoindolyl, 3-isoindolyl, and carbazoyl.

An alkyl group of the present dithioesters is a saturated hydrocarbon ina molecule that is bonded to one other group in the molecule through asingle covalent bond from one of its carbon atoms. Examples of alkylgroups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyland tert-butyl. An alkoxy group is an alkyl group where an oxygen atomconnects the alkyl group and one other group (e.g., the alkyl group andthe dithioester carbon). An alkylene group is a saturated hydrocarbon ina molecule that is bonded to two other groups in the molecule throughsingle covalent bonds from two of its carbon atoms. Examples of alkylenegroups include methylene, ethylene, propylene, iso-propylene(—CH(CH₂)CH₂—), butylene, sec-butylene (—CH(CH₃)CH₂CH₂—), andtert-butylene (—C(CH₃)₂CH₂—). An azaalkylene group is a saturatedhydrocarbon comprising one or more nitrogen atoms in the chain in amolecule that is bonded to two other groups in the molecule throughsingle covalent bonds from two of its carbon atoms.

Alkyl, oxyalkyl, alkylene, azaalkylene, aromatic and heteroaromaticgroups can be substituted with functional groups including, for example,halogen (—Br, —Cl, —I and —F) —OR″, —CN, —NO₂, —NH₂, —NHR″, —NR″₂,—COOR″, —CONR″₂, and —SO_(k)R″ (k is 0, 1 or 2). Each R″ isindependently —H, an alkyl group, a substituted alkyl group, a benzylgroup, a substituted benzyl group, an aromatic group or a substitutedaromatic group. A substituted aromatic or heteroaromatic group can alsohave an alkyl or substituted alkyl group as a substituent. A substitutedalkyl group can also have an aromatic or substituted aromatic group as asubstituent. A substituted alkyl, oxyalkyl, alkylene, azaalkylene,aromatic or heteroaromatic group can have more than one substituent. Asubstituent should not appreciably interfere with a polymerization. Forinstance, a primary or secondary amine can react with and inactive adithioester. Other acceptable functional groups include epoxy, hydroxy,alkoxy, acyl, acyloxy, carboxy, sulfonate, alkylcarbonyloxy, isocyanato,cyano, silyl, halo, and dialkylamino, each of which can undergo furtherchemical transformation, such as being joined with another polymerchain.

Alkali metal ions include lithium, sodium, and potassium ions. Alkalineearth metal ions include magnesium and calcium ions. Halides includefluoride, chloride, bromide, and iodide.

EXEMPLIFICATION Example 1 Preparation ofPoly(2-acrylamido-2-methylpropanesulfonate [AMPS]) andPoly(3-acrylamido-3-methylbutanoate [AMBA])

Anionic AMPS and AMBA homopolymers were synthesized in water by RAFT.4,4′-azobis(4-cyanopentanoic acid) was the initiator and4-cyanopentanoic acid dithiobenzoate was the RAFT chain transfer agent(CTA). The reactions were carried out at 70° C. under a nitrogenatmosphere, in round-bottomed flasks, equipped with a magnetic stir barand sealed with a rubber septum. The initiator:CTA ratio was 5:1 on amolar basis. The monomer concentration was 2.0 M. The solution pH wasadjusted to ˜9.6±0.2 (such that AMBA was fully ionized). Aliquots (0.74mL) were removed from the polymerizations, via syringe, approximatelyevery hour, diluted 100 fold with eluent and then characterized byaqueous size exclusion chromatography (ASEC) (20% MeCN/80% 0.1 M NaNO₃eluent, Viscotek TSK Viscogel column, Spectraphysics UV2000 detector, HP1047A RI detector, poly(sodium 4- styrenesulfonate) standards). Theresults for the synthesis of the AMPS and AMBA homopolymers aresummarized in Table 1.

TABLE 1 Time Conver- M_(n) M_(n) M_(w) M_(w)/ Sample (min) sion (%)(theory) (expt)^(a) (expt)^(a) M_(n) ^(a) AMPS1 255 77.1 26,500 24,40031,500 1.29 AMPS2 343 88.0 17,600 19,500 22,600 1.16 AMPS3 8 >95.0^(a) —— — — AMBA1 255 65.5 21,800 14,000 18,200 1.30 AMBA2 346 74.8 15,00012,100 14,800 1.22 AMBA3 8 >95.0^(a) — — — — PAMPS — — — 33,900 38,6001.14 macro-CTA P(AMPS- — — 68,500 69,700 79,500 1.14 b-AMBA) PAMBA — — —31,300 35,300 1.14 macro-CTA P(AMBA- — — 64,400 57,900 67,200 1.16b-AMPS) ^(a)As determned by aqueous size exclusion chromatography,calibrated with poly(sodium 4-styrenesulfonate) standards in 20%MeCN/80% 0.1 M NaNO₃ eluent.

The CTA:monomer ratios were such that the theoretical M_(n), at 100%conversion, for AMPS1 was 34,400 g/mol and 20,000 g/mol for AMPS2. Asingle AMPS homopolymer (AMPS3) was also synthesized by conventionalfree radical polymerization as a control. The experimental details werethe same as the RAFT polymerizations except CTA was not added. In thisinstance, the reaction solution gelled within ˜10 min. AMBA homopolymerswere synthesized under identical conditions as the AMPS homopolymers andsimilar results were obtained.

AMPS and AMBA homopolymers were subsequently employed as macro-CTAs forthe block copolymerization of the opposite monomer (i.e. RAFT mediatedPoly(AMPS) was used as the macro-CTA for the RAFT polymerization ofAMBA, yielding a diblock copolymer of poly(AMPS-block-AMBA), andvice-versa). Due to the high viscosities of the aqueous solutions ofmonomer and macro-CTA, the monomer concentration was reduced to 1.0 Mfor the block copolymerizations as opposed to the 2.0 M concentrationsused in the preparation of the homopolymers. Given the lower monomerconcentration polymerization times were extended to approximately 13 has compared to 6.5 h for the homopolymerizations. Proton NMR wasconducted and the peaks were assigned for the homopolymers of AMPS andAMBA, as well as the corresponding poly(AMPS-block-AMBA) copolymer.

The copolymer was seen to be composed of monomeric units derived fromboth AMPS and AMBA. Integration of the peaks associated with themethylene protons adjacent to the anionic functionalities yielded acopolymer composition of 46:54 (mol % basis) (AMPS:AMBA). This was inexcellent agreement with the theoretical target composition of 45:55.Likewise the block copolymer composition for the AMBA-AMPS diblock wasfound to be 49:51, with a target theoretical composition of 47:53.

Also listed in Table 1 is a summary of the molecular weights andpolydispersities for the macro-CTAs and the corresponding blockcopolymers. Molecular weight distributions were determined using aViscotek TRISEC detector, calibrated with poly(4-sodiumstyrenesulfonate) standards in the eluent described above. Data analysiswas performed using software written in-house.

Example 2 Synthesis of N,N-dimethyl-s-thiobenzoylthiopropionamide

The title compound was synthesized in a manner similar to that reportedby Bhandari, C. S.; Mahnot, U. S.; Sognani, N. C. Journal Für PraktischeChemie 1971, 313, 849. To a 100 mL round-bottomed flask was added2-mercaptopropionic acid (50.0 mL, 0.56 mol). Dimethylamine (23.9 g,0.53 mol) was added to the solution while keeping the reaction flask ina water bath. Excess dimethylamine was removed using a water aspirator.The reaction was heated at 110° C. for an extended period, during whichtime the reaction took on a light yellow color. The product wasfractionally distilled under reduced pressure. The major crude fraction,which was collected at approximately 80° C. (0.02 mmHg), was determinedto contain 57% of the target compound and 43% acid precursor. The acidimpurity was removed by washing with dilute NaOH/CH₂Cl₂. The CH₂Cl₂ wasremoved using a rotary evaporator and the target compound purified byvacuum distillation (bp 80° C. at 0.02 mmHg). Yield=45%. ¹H NMR (CDCl₃)δ (ppm) 1.53 (d, —CH₃), 2.11 (s, —SH), 2.99 (s —CONCH₃), 3.16 (s—CONCH₃), 3.67 (m —CH).

Carboxymethyl dithiobenzoate (5.00 g, 23.60 mmol) was mixed withdeionized water (20 ml) and neutralized with a dilute solution of sodiumcarbonate to a final volume of 130 ml. Subsequently,N,N-dimethyl-2-mercaptopropionamide (3.13 g, 15.0 mmol) was added to thesodium carboxymethyl dithiobenzoate solution. After 24 hours thecontents of the flask were poured into a separatory funnel and a darkred oil isolated. The aqueous phase was washed with diethyl ether (30.0mL) to extract the remaining product. Subsequently, the products weredissolved in diethyl ether (50.0 mL) and washed with deionized H₂O (25.0mL). The diethyl ether phase was separated and dried over anhydroussodium sulfate. The solution was filtered and the solvent removed via arotary evaporator. The product was isolated as deep orange plates byrecrystallization from a mixture of methanol/water (3:2 v/v). Yield=52%.Melting point=61-62° C. ¹H NMR (d₆-DMSO) δ (ppm): 1.52 (d, —CH₃) 2.88(s, —N—CH₃), 3.08 (s, —N—CH₃), 5.04 (m —CH), 7.50, 7.66, 7.96 (m, —CH).¹³C NMR (d₆-DMSO) δ (ppm): 16.54 (CH₃), 35.46 (N—CH₃), 36.86 (N—CH₃),47.15 (CH), 126.42, 128.70. 133.04, 143.71 (CH), 169.02 (C═O), 226.46(CS₂). IR (KBr Disc): 1643.1 (C═O); 1039.9 (C═S). CHNS elementalmicroanalysis for C₁₂H₁₅NOS₂—Calculated: C, 56.88%; H, 5.97%; N, 5.53%;S, 25.31%. Found C, 56.89%; H, 5.74%; N, 5.48%; S, 25.19%.

In FIG. 1 are shown the SEC chromatograms (RI response) for aliquots ofthe polymerization at various time intervals (FIG. 1 a), along with thekinetic plot (FIG. 1 b) and the molecular weight vs. conversion andpolydispersity vs. conversion plots (FIG. 1 c).

The SEC chromatograms in FIG. 1 a clearly show the increase in molecularweight with time. Also noted is the appearance of a higher molecularweight species -evidenced as shoulder, at extended polymerization time.The kinetic plot in FIG. 1 b show 1^(st) order behavior, implying aconstant number of radicals. The number average molecular weightincreased in a linear fashion with conversion (FIG. 1 c), at least up toapproximately 60%, and is characteristic of a controlled or livingprocess. The polydispersity showed an initial decrease with increasingconversion and then began to increase slightly. At all times thepolydispersity remained low (M_(w)/M_(n)<1.25)—well below thetheoretical lowest limit of 1.50 for a conventional free radicalpolymerization.

Example 3 Synthesis of N,N-dimethyl-s-thiobenzoylthioacetamide

N,N-Dimethyl-2-mercaptoacetamide was synthesized in a similar fashion toN,N-dimethyl-2-mercaptopropionamide. 2-Thioglycolic acid (50.0 ml, 0.563mol) was reacted with dimethylamine (23.9 g, 0.53 mol) in the mannerreported above. The reaction was allowed to proceed at 110° C. for 5days. The product was then distilled and purified. The product waspurified via vacuum distillation (bp 112° C. at 1.0 mmHg). Yield=68%. ¹HNMR (CDCl₃) δ (ppm) 2.41 (s, —SH), 2.99 (s —CONCH₃), 3.08 (s —CONCH₃),3.36 (m —CH₂).

Carboxymethyl dithiobenzoate (30.22 g, 142.0 mmol) was neutralized witha dilute aqueous solution of sodium carbonate.N,N-dimethyl-2-mercaptoacetamide (16.28 g, 15.0 mmol) was subsequentlyadded to the sodium carboxymethyl dithiobenzoate solution. The reactionwas allowed to proceed for 24 h. The product was subsequently extractedwith diethyl ether and dried over anhydrous sodium sulfate. The solutionwas filtered and the solvent removed via a rotary evaporator. Theproduct was isolated as deep orange needles by recrystallization from amixture of methanol/water (3:2 v). Yield=57%. Melting point 63-64° C. ¹HNMR (d₆-DMSO) δ (ppm): 2.88 (s, —N—CH₃), 3.12 (s, —N—CH₃), 4.48 (s—CH₂), 7.50, 7.66, 7.98 (m, —CH). ¹³C NMR (d₆-DMSO) δ (ppm): 35.29(N—CH₃), 36.98 (N—CH₃), 41.008 (CH₂), 126.35, 128.66, 132.88, 144.23(CH), 165.20 (C═O), 227.29 (CS₂). IR (KBr Disc): 1654.6 (C═O); 1045.3(C═S). CHNS elemental microanalysis for C₁₁H₁₃NOS₂—Calculated: C,55.20%; H, 5.47%, N, 5.85%, S, 26.79%. Found C, 55.11%; H, 5.37%; N,5.84%; S, 26.86%.

Example 4 RAFT Polymerization of N,N-Dimethylacrylamide

Polymerizations of N,N-dimethylacrylamide (DMA) in benzene wereconducted at 60° C. in flame sealed ampoules equipped with magnetic stirbars, whereas polymerizations in d₆-benzene were performed in flamesealed NMR tubes. All polymerizations were performed at monomerconcentrations of ˜1.93 M in benzene, with AIBN as the free radicalinitiator. The chain transfer agent wasN,N-dimethyl-s-thiobenzoylthiopropionamide orN,N-dimethyl-s-thiobenzoyl-thioacetamide. Polymerizations at a CTA/Iratio of 5/1, in d₆-benzene, were performed at an initiatorconcentration of 9.52×10⁻⁴ mol, for a target molecular weight of 40,000.Similarly, the polymerizations conducted at a CTA/I ratio of 80/1, inbenzene, were performed at an initiator concentration of 6.28×10⁻⁵ mol,for a target molecular weight of 40,000. The ampoules were subjected tothree freeze-pump-thaw cycles to remove oxygen from the DMA solutionsand were subsequently placed in a pre-heated water-bath or inserted intothe DMR spectrometer with the temperature maintained at 60° C.Termination of the polymerizations was achieved by freezing thereactions in a dry ice/acetone bath. The polymers were isolated byprecipitation into hexane, filtered, redissolved in THF andre-precipitated into hexane. Conversions were determined gravimetrically(polymerizations at a CTA/I ratio of 80/1) or by ¹H NMR spectroscopy(polymerizations at a CTA/I ratio of 5/1).

Example 5 A Comparative Study of the Raft Polymerization of DMA in thePresence of CTAs (1a-benzyl dithiobenzoate (BDB), 1b-isopropyl cumyldithiobenzoate (CDB), 1c-N,N-dimethyl-s-thiobenzoylthiopropionamide(TBP), 1d-N,N-dimethyl-s-thiobenzoylthioacetamide (TBA))-

RAFT polymerizations of N,N-dimethylacrylamide (DMA) were conducted inbenzene at 60° C. using AIBN as the initiator. Polymerizations wereperformed in degassed, flame sealed glass reactors in order to precludeany possible oxidation of the CTAs. Pertinent data including CTA/Iratios, reaction times, conversions, and molecular weights are given inTable 2.

TABLE 2 Data from the RAFT polymerization of DMA with CTAs 1a 1d (targetMW = 40,000) in d₆-benzene (60° C.) using a CTA/I ratio of 5/1: [M] =1.92, [CTA] = 4.81 × 10⁻³, [I] = 9.52 × 10⁻⁴. Time % CTA (h) ConversionMn_(Th) Mn_(SEC) ^(B) M_(W)/M_(n) 1a 14.5 80 32,000 50,700 1.22 1a 36.690 36,000 51,200 1.22 1a 66.5 97 38,800 53,200 1.24 1a 156.0 98 39,20055,300 1.27 1a 181.5 98 39,200 59,700 1.23 1a 186.2 98 39,200 60,0001.24 1b 8.1 59 23,600 35,800 1.12 1b 36.6 86 34,400 45,800 1.25 1b 66.595 38,000 54,600 1.24 1b 156.0 96 38,400 53,100 1.24 1b 181.5 96 38,40053,400 1.25 1b 186.2 96 38,400 55,700 1.26 1c 19.0 78 31,200 35,200 1.141c 36.6 82 32,800 42,600 1.14 1c 66.5 93 37,200 48,500 1.19 1c 156.0 9437,600 49,100 1.15 1c 186.2 95 37,992 53,400 1.18 1d 10.9 67 26,80039,400 1.15 1d 36.6 82 32,800 47,900 1.20 1d 66.5 96 38,400 49,600 1.241d 156.0 97 38,800 53,300 1.23 1d 181.5 98 39,200 53,350 1.24 1d 186.298 39,200 55,700 1.23 ^(a)As determined by ¹H NMR spectroscopy, recordedin d₆-benzene. ^(b)SEC in DMF at room temperature, at a flow rate of 0.5ml/min, with ×2 PL Mixed-D columns, PL UV-1200, Optilab RI and DAWN EOSdetectors.In order to follow kinetics at short reaction times (and thus evaluateany effects of CTA structure on the pre-equilibrium in Scheme 1) aseries of comparative polymerizations were monitored directly by NMRspectroscopy. CTA/I ratios of 5/1 were utilized with the temperatureheld constant at 60° C. in d₆-benzene. The spectra were obtained at15-minute intervals for nine hours, with a data acquisition time of 108seconds. Conversions at longer time intervals were followed by analyzingaliquots of identical solutions taken from separate flame-sealedampoules heated in a water bath at 60° C. Polydispersities and absolutemolecular weights were determined by size exclusion chromatography inDMF utilizing inline RI, TV and MALLS detectors.

FIG. 2 illustrates the respective kinetic plots for the polymerizationof DMA with CTAs 1a-1d. The importance of reinitiation followingfragmentation in the pre-equilibrium was demonstrated by the notabletime intervals required to reach a constant slope in the respective1n(M_(o)M₁) vs. time plots. These times were approximately 25 minutesfor the novel CTAs 1c and 1d, compared to approximately 80 and 100minutes for 1a and 1b respectively. This order was in agreement withthat expected for reinitiation based on radical reactivity alone. Themore stable, bulky cumyl radical from 1b should add to DMA slower thanthe primary benzyl radical from 1a and significantly slower than theacetadmido radicals from 1c and 1d. This was also consistent with thepublished reactivity ratios r₁ and r₂ for the styrene/DMA pair of 1.37and 0.49 respectively.

In any event, once the pre-equilibrium phase of the RAFT process wasreached, polymerizations with all four CTAs exhibited a 1^(st) orderrelationship between monomer conversion and polymerization time, atleast up to moderately long polymerization times (FIG. 2). This firstorder relationship was maintained in the respective systems up toapproximately 55% conversion, after which the rates decreased. Thebreakdown in “livingness” of these polymerizations, like othercontrolled free radical processes, was indicative of bimoleculartermination events. These events were greatly suppressed by increasingthe CTA/I ratio.

The theoretical molecular weights (Mn_(th)) for the polymerizations atCTA/I ratios of 5/1 ranging from 14 to 186 hours are listed in Table 2.The Mn_(th) values, which were determined using Equation 1, are shownalong with the experimentally determined molecular weights (Mn_(SEC)).

$\begin{matrix}{{MW}_{Th} = {{\lbrack \frac{\lbrack M\rbrack \times {MW}_{monomer}}{\lbrack{CTA}\rbrack} \rbrack \times \%\mspace{14mu}{Conversion}} + {MW}_{CTA}}} & (1)\end{matrix}$

It was seen that the latter diverged dramatically from the former withconversion. When comparing the four CTAs at specific reaction time, thebest correlation between the Mn_(SEC) and the Mn_(Th) was observed with1c. This result was indicative of the importance of the events that tookplace early in the RAFT mechanism. The similarity between 1c and themonomer allowed all chains to be started early in the RAFTpolymerization. For CTAs 1a and 1b, the differences between Mn_(Th) andMn_(SEC) were slightly higher. This result was again consistent withthose reported by Moad, G.; Chiefari, J.; Chong, Y. K.; Krstina, J.;Mayadunne, R. T. A.; Postma, A.; Rizzardo, E.; Thang, S. H. Polym. Int.2000, 49, 993, for the polymerization of styrene with 1b.

Table 2 indicates that the conversion rates at extended time decreaseddramatically due to a reduction in the number of active chains and thelow concentration of monomer. Chromatograms, see FIGS. 3B-3D, from theDMA polymerizations using CTAs 1b-1d show evidence of bimolecularradical coupling as determined by the presence of high molecular weightshoulders. Using a MALLS detector it was determined that these shouldershave molecular weight values approximately twice that of the main peaks.In addition, the relative amounts of the high molecular weightimpurities increased with increasing conversion. Although notquantified, it appears that PDMA synthesized using 1b-1d containedapproximately similar numbers of dead chains, see FIG. 3B-D. These sidereactions can be avoided simply by limiting the conversion to less than50% or by increasing the CTA/I ratio.

Example 6 RAFT Polymerization of N,N-Dimethylacrylamide in Water

DMA homopolymers were synthesized in water via RAFT. Both sodium4-cyanopentanoic acid dithiobenzoate (CTPNa) andN,N-dimethyl-s-thiobenzoylthiopropionamide (TBP) were employed as theRAFT chain transfer agents (CTAs). CTPNa was chosen due to its inherentwater-solubility and its ability to mediate the controlledpolymerization of anionic acrylamido monomers in aqueous media, whileTBP was selected since the effectiveness of this CTA for thepolymerization of DMA in organic media has recently been demonstrated.4,4′-Azobis(4-cyanopentanoic acid) (V-501) was utilized as the freeradical initiator in all instances, with the CTA/I ratio held constantat 5/1 ([Monomer]=1.83 M, [V-501]=9.2×10⁻⁴ M, [CTA]=4.57×10⁻³ M). TheCTA/monomer ratios were chosen such that the theoretical M_(n) at 100%conversion would be 40,000. The polymerization solutions were purged for30 min with nitrogen to remove oxygen. The solutions were thentransferred via cannula to individual rubber septa-sealed, glasstest-tubes which were pre-purged with nitrogen. The test-tubes wereimmersed in a pre-heated water-bath at three different temperatures: 60,70 and 80° C. The test tubes were removed from the water baths aftervarious time intervals. Polymerizations were allowed to proceed for atotal of 9.5 h. After removal from the water bath, the samples wereimmediately cooled in ice water and stored in a freezer until analysis.

The samples were analyzed by NMR spectroscopy (using a water-suppressiontechnique) to determine conversion. A portion of each sample wasdiluted, and analyzed by aqueous size exclusion chromatography (ASEC)(using an eluent of 20% acetonitrile/80% 0.05 M Na₂SO₄, a Viscotek TSKViscogel (4000PW×L) column, and Polymer Labs LC 1200 UV/Vis, WyattOptilab DSP Interferometric refractometer, and Wyatt DAWN EOS multiangle laser light scattering detectors). The dn/dc of PDMA in the aboveeluent was determined to be 0.1645 at 25° C. The molecular weight andpolydispersity data were determined using the Wyatt ASTRA SEC/LSsoftware package.

FIG. 4 shows an example of the evolution of molecular weight, asdetermined by ASEC on direct aliquots from the PDMA homopolymersynthesized using CTPNa at 80° C. An increase in the molecular weight(peak shifts to shorter retention times) was observed which was, atleast qualitatively, indicative of a controlled polymerization. There isevidence in the chromatograms, at T>160 min, of a small amount of highmolecular weight species arising from uncontrolled polymerization ortermination events (high molecular weight shoulder). This was notobserved in chromatograms of the TBP-mediated polymerization at the sametemperature (see insert).

The kinetic plots for the CTPNa and TBP-mediated polymerizations of DMAutilizing the 5/1 ratio of CTA/I are shown in FIG. 5. The CTPNa-mediatedpolymerizations (solid symbols) showed the expected increases in ratewith increasing temperature. Successful polymerization in the presenceof TBP (open triangle) in water occurred only at the higher temperatureof 80° C. with much lower rates of monomer incorporation at 60 and 70°C. (data not shown).

The molecular weight versus conversion data for the CTPNa andTBP-mediated polymerizations of DMA are shown in FIG. 6. The plots inwater alone for TBP at 80° C. and CTPNa at 60, 70 and 80° C.,respectively, are linear and exhibit identical slopes, though the formerhas a non-zero intercept. Addition of sufficient quantities of DMF tothe aqueous solutions during polymerization resulted in a remarkablylinear relationship between experimentally determined molecular weightand conversion for CTPNa and TBP mediated polymerizations. This can becompared to the theoretical projection of molecular weight versusconversion (dotted line in FIG. 6) of an ideal RAFT polymerization.Controlled chain growth was realized at all three temperatures withCTPNa and at 80° C. with TBP. Molecular weights were somewhat higherthan theoretically predicted possibly due to underlying non-RAFTpolymerization and/or radical coupling inherent to CRP processes.Addition of DMF to aqueous solutions of TBP results in better molecularweight control (Table 3). It is also clear from Table 3 that M_(w)/M_(n)values ranging from 1.11 to 1.23 are well within the limits consideredfor controlled polymerizations.

TABLE 3 Temp Time Conversion M_(n) M_(n) CTA (° C.) (min) (%)^(a)Theory^(b) Expt^(c) M_(w)/M_(n) ^(c) TBP 60 580 1 400 7,400 1.67 TBP 70580 25 10,000 30,600 1.17 TBP 80 160 66 26,400 43,500 1.14 TBP 80 160 6626,400 39,300 1.14 (0.9 M DMF) TBP 80 160 68 27,200 34,700 1.23 (1.8 MDMF) TBP 80 160 69 27,600 34,400 1.20 (3.6 M DMF) CTPNa 60 160 48 19,20025,560 1.11 CTPNa 70 160 80 32,000 41,130 1.15 CTPNa 80 160 87 34,80045,570 1.14 ^(a)As determined by NMR spectroscopy. ^(b)Mn_(theory) ={([M] × MW_(mon))/[CTA]) × %Conversion} + MW_(CTA). ^(c)As determined byASEC in 20% MeCN/80% 0.05 M Na₂SO₄ employing RI and light scatteringdetectors.

Example 7 Synthesis of dithiobenzoic acid, 2-(2-pyridinyl)ethyl ester

The crude product of newly synthesized dithiobenzoic acid (0.5 moltheoretically) was dissolved in benzene and placed in a round bottomflask equipped with a vigreaux column and magnetic stirbar. The reactionvessel was purged with nitrogen for 1 hour. Freshly distilled2-vinylpyridine was added via syringe (43 ml, 0.4 mol) at 0° C. Thereaction was then heated to reflux and allowed to react overnight. Theviscous liquid that remained after the solvent was removed was thenpurified by column chromatography with neutral alumina as the stationaryphase and 3/2 v/v methylene chloride/hexane as the mobile phase. Thesolvent was then removed from the red-orange fraction in vacuo anddiethylether was added to the remaining liquid resulting in theprecipitation of a slightly yellow solid. The liquid phase was retainedand after solvent removal in vacuo the desired product was obtained asan red-orange liquid. Structure was confirmed by from ¹H, ¹³C, and ¹³CDEPT N.M.R. spectroscopy.

Example 8 Synthesis of dithiophenylacetic acid, 2-(2-pyridinyl)ethylester

The crude product of newly synthesized dithiophenyl acetic acid (10 g,59 mmol theoretically), freshly distilled 2-vinylpyridine (6.25 g, 59mmol), and 1 mol % toluene sulfonic acid were dissolved in benzene andplaced in a round bottom flask equipped with a vigreaux column andmagnetic stirbar. The reaction was then heated to reflux and allowed toreact for 16 hours. The viscous liquid that remained after the solventwas removed was then purified by column chromatography (silica 2/1 v/vhexane/ethyl acetate). Yield=3.9 g. ¹ H NMR (CDCl₃) δ=3.042 (t, 2 H),δ=3.573 (t, 2 H), δ=4.233 (s, 2 H) δ=6.968-7.476 (m, 8 H), δ=8.467, (d,1 H). ¹³C NMR (CDCl₃) δ=35.627 (CH₂), δ=36.180 (CH₂), δ=58.323 (CH₂),δ=121.932 (CH), δ=123.383 (CH₂), δ=127.501 (CH), δ=128.818 (CH),δ=129.346 (CH), δ=137.272 (C), δ=149.668 (CH), δ=159.305 (C), δ=235.369(C═S).

Example 9 Synthesis of carbonodithioic acid, O-ethylS-(2-pyridinylmethyl)ester

1.00 g (3.9 mmol) of 2-(bromomethyl)pyridine hydrobromide and 0.36 g(3.9 mmol) of O-ethyldithiocarbonic acid, potassium salt were combinedin a 50 ml round bottom flask with 20 ml of 100% ethanol. The reactionvessel was sealed with a rubber septum and oxygen was removed by severalfreeze-pump-thaw cycles. The reaction mixture was then warmed to roomtemperature and allowed to stir under positive nitrogen pressure. Awhite precipitate was observed after the first few minutes of thereaction. The reaction was allowed to stir for an additional 20 hours.20 mL of 0.5M aqueous sodium hydroxide was then added causing thereaction mixture to become homogenous and take on a red color.Extraction with hexane after addition of an additional 20 ml of thesodium hydroxide solution yielded a fluorescent yellow-green solution.Hexane was removed and the residue was passed over a silica column(ethyl acetate as the elluent). The final product appears as ayellow-green liquid and fluoresces blue when exposed to long wavelengthultra-violet light. Yield=0.342 g (39%). ¹ H NMR (CDCl₃) δ=1.212 (t, 3H), δ=4.353 (s, 2 H), δ=4.47 (q, 2 H), δ=7.002 (t, 1H), δ=7.234 (d, 1H), δ=7.466 (t, 1 H), δ=8.377 (d, 1 H). ¹³C NMR (CDCl₃) δ=13.929,δ=42.135, δ=70.358, δ=122.494 (CH), δ=123.424 (CH), δ=136.777 (CH),δ=149.660 (CH), δ=156.152 (C), δ=213.730 (C═S).

Example 10 Synthesis of dithiodiphenylacetic acid, 2-(2-pyridinyl)ethylester

Dithiodiphenylacetic acid was dissolved in benzene in a round bottomflask equipped with a vigreaux column and magnetic stir bar. 2-Vinylpyridine was then added via syringe under nitrogen at room temperature.The reaction mixture was then brought to reflux and reacted for 5 hours.The reaction was allowed to cool to room temperature and extracted withportions of aqueous HCl at 0° C. until the aqueous phase remainedcolorless. The aqueous phases, which appear green when acidic, were thencombined and washed with diethyl ether. Finally diethyl ether andaqueous sodium hydroxide were added at 0° C. until the color of themixture became orange (pH ˜12). The basic aqueous phase was extractedwith portions of diethyl ether until the organic phase remainedcolorless. The solvent was then removed from the combined organic phasesin vacuo and the remaining dark orange oil was purified by columnchromatography with silica gel (acetone) followed by a secondpurification by column chromatography (silica gel/dichloromethane).Evaporation of the solvent yielded the desired compound as a pale orangesolid. ¹ H NMR (CDCl₃) δ=3.113 (t, 2 H), δ 3.654 (t, 2 H), δ=5.895 (s, 1H), δ=7.074-8.535 (19 H). ¹³C NMR (CDCl₃) δ=35.336 (CH₂), δ=35.805(CH₂), δ=70.746 (CH), δ=121.649 (CH), δ=123.133 (CH), δ=127.226 (CH),δ=128.300 (CH), δ=129.105 (CH), δ=136.427 (CH), δ=140.562 (C), δ=149.402(CH), δ=159.089 (CH), δ=237.770 (C═S).

Example 11 Synthesis of naphthyl dithiocarbonylthio CTA

11.01 g (0.07003 mol) of methyl-2-mercaptopropionate was mixed with12.29 g (0.07817 mol) naphthylmethylamine in a 50 mL 1 neck round bottomflask equipped with a magnetic stir bar. The flask was purged withnitrogen. The reaction was heated to 145° C. for 4 hours. The reactionwas allowed to cool to room temperature and subjected to a full vacuumto remove the unreacted thiol methyl ester. Since the absence of thiolpeaks upon ¹H NMR analysis indicated disulfide formation, a reduction ofthe naphthyl thiol product in ethanol was performed using sodiumborohydride. The reduction procedure is analogous to that used byD′amico. The product was dissolved in 210 mL of ethanol and heated to70° C. under nitrogen. To this mixture, a solution of NaBH₄ (2.64 gramsin 140 mL of ethanol) was added. The temperature was raised to 80° C.for one hour. The reaction was cooled to room temperature, and 1 L ofice was added. The pH was then lowered to 3 using concentrated HCl. Theprecipitated solid naphthyl thiol was collected using a Buchner funnel,washed with deionized water, and dried in a vacuum oven. The product waspurified by recrystallization using a mixture of acetone and hexane toyield white crystals. Yield=61%. MP: 125 to 127° C.

10.00 g (0.04076 mol) of the Naphthylthiol and 26.12 g (0.1230 mol) of2-(thiobenzoyl)thioglycolic acid were dissolved with a mixture of 350 mLof methylene chloride and 275 mL benzene. Once the reactants weredissolved, 100 mL of deionized H₂O was added. The contents were placedin a 1 L 3 neck round bottom flask equipped with a stir bar. Thereaction solution was purged with nitrogen for 30 min. The water waschanged daily for one week. The water added was purged with nitrogenbefore addition. The organic phase was separated and the solvent wasremoved via a rotary evaporator to yield a pink solid. The compound waspurified by recrystallization from a mixture of hexane and chloroformyielding a light pink solid. Yield=75.1%.

Example 12 Synthesis of dansyl dithiocarbonylthio CTA

N-(2-Aminoethyl)-5-(dimethylamino)-1-naphthalene-sulfonamide (2.51 g,9.605 mmol) was mixed with of methyl-2-mercaptopropionate (1.86 g, 15.37mmol) in a 50 mL 1 neck round bottom flask equipped with a magnetic stirbar. The reaction was heated to 145° C. and heated for 2 hours. Thereaction was allowed to cool to room temperature and subjected to a fullvacuum to remove the unreacted thiol methyl ester.

The absence of thiol peaks upon ¹H NMR analysis indicated disulfideformation, the product was reduced using NaBH₄ using the followingprocedure. To the crude product was added 17 mL of absolute EtOH in a 50mL 1 neck round bottom flask. The solution was purged with nitrogen andheated to 80° C. NaBH₄ (0.4330 g) was mixed with 17 mL of EtOH andpurged with nitrogen. The mixture was heated to 80° C. and slowlytransferred into the dansyl solution. The solution was left to react for1 hour, and allowed to cool to room temperature. To the reactionproducts 50 mL of ice was added. The mixture became cloudy and a yellowppt formed on the glass. The pH of the solution was lowered to 3 and thesolution became clear. The pH was raised to approximately 8.5, uponwhich the aqueous phase became cloudy again. The aqueous phase wasextracted twice with 50 mL of chloroform using a 150 mL sep funnel. Thechloroform was removed via rotary evaporator off leaving a yellow/greenoil of the dansylamide thiol. Yield=96%.

The dansylamide thiol 4.18 g (0.03297 mol) was mixed with 40 mL ofdiethyl ether. S-(Thiobenzoyl)thioglycolic acid (7.00 g, 0.010 mol) wasmixed with 50 mL of deionized H₂O and neutralized to a final pH of 7.5using a dilute NaOH solution to a final volume of 100 mL. The twosolutions were mixed in a 1 neck 150 mL round bottom flask with stirbar, yielding a two-phase mixture. The reaction vessel was kept in thedark and allowed to stir for one week. After one week, the etherealphase had taken on a dark orange color. The ethereal phase wasseparated, washed twice with DIH₂O and dried with anhydrous sodiumsulfate. The product was purified by column chromatography on silica gelin a mixed solvent system of acetone and methylene chloride (10:90). ¹HNMR (d₆-DMSO) δ (ppm): 1.34 (m, CH₂—CH₂), 1.56 (m, CH), 2.76 (t,CH₂—NCO), 2.81 (s, —N(CH₃)₂), 2.94 (CH₂—NSO₂), 4.66 (s, CH₃), 7.23-8.44(m, 11H ArH). ¹³C NMR (d₆-DMSO) δ (ppm): 17.5 (CH₃), 25.93 (CH₂), 26.65(CH₂), 38.38 (CH₂), 42.12 (CH₂), 45.13 (—N(CH₃)₂), 50.59 (CH—S),115.11-151.35 (16C, ArC), 169.21 (CO), 226.89 (CS).

Example 13 Synthesis of N,N′-Ethylenebis(s-thiobenzoylthio)propionamide

This reaction was performed as previously reported by Atkinson, E.;Richard, H.; Bruni, J.; Granchelli, F. J. Med. Chem. 1965 8(1), 29-33.Methyl-2-mercaptopropionate (33.77 g, 0.2858 mol) was mixed with 5.05 gof ethylenediamine (0.08402 mol) in a 50 mL 1 neck round bottom flaskequipped with a magnetic stir bar. The vessel was purged with nitrogen.The reaction vessel was heated to 145° C. for three hours. The contentswere subjected to a full vacuum for one hour to remove excess thiol. Themelting point of the white solid product was determined to be between190-192° C. Yield=99% of N,N-ethylenebis(2-mercaptopropionamide). Theabsence of thiol peaks upon ¹H NMR analysis indicated polymericdisulfide formation. The product was reduced using an aqueous solutionof 0.1 M NaOH and not purified further.

3.15 grams (0.01323 mol) of N,N′-ethylenebis(2-mercaptopropionamide) wasmixed with 30 mL of deionized H₂O. The solid was not miscible withwater. The pH of the solution was raised until the compound becamesoluble. The final pH was adjusted to 9.4 at a final volume of 100 mL.The solution was then purged with nitrogen and the pH was lowered to7.4. The solution was purged a second time and the mixture was addeddirectly to a solution of sodium s-(thiobenzoyl)thioglycolate [8.63 g,(40.65 mmol) of the acid neutralized to a pH of 7.5 to a total volume of100 mL]. Immediately, the solution became a cloudy orange color. After afew minutes, a dark precipitate started to collect. The product wasplaced in a refrigerator for four days. The aqueous phase was a clearorange color. A dark precipitate was formed at the bottom of the flask.Filtering with a fritted glass funnel isolated a pink solid. The productwas broken up using a mortar and pestle and dissolved with 150 mL ofmethanol. Water was added until the mixture just became cloudy. Thesolution was placed in the freezer overnight. The precipitated pinksolid was collected via filtration and dried in a vacuum oven for threehours. The compound was purified by column chromatography on silca gelusing a mixed solvent system of ethyl ether/methylene chloride (60:40).Yield=57.72% yield. M.P.=116-118° C. ¹H NMR in CDCl₃ (TMS ref): 1.55 (d,—CH₃) 3.30 (s, —CH₂—N) 4.56 (m, —CH) 6.74 (s, —NH) 7.31, 7.48, 7.92 (m,CH). ¹³C NMR: 15.22 (CH₃) 38.85 (NH—CH2) 47.50 (CH) 126.13, 127.44,132.07 (CH) 143.08 (C) 170.28 (C═O) 226.23 (CS₂).

Example 14 Preparation of Low Polydispersity poly(N,N-dimethylacrylamide) Using N,N-dimethyl-s-thiobenzoylthiopropionamide

N,N-Dimethyl-s-thiobenzoylthiopropionamide (127.46 mg) was weighed intoa 20 mL scintillation vial and N,N-dimethyl acrylamide (19.983 g) wasadded to the scintillation vial. The mixture was transferred to a 100 mLvolumetric flask and made to the mark with distilled deionized water. A4.8 mL aliquot of a stock solution of 4,4′-Azobis(4-cyanopentanoic acid)(2.01×10⁻² M) was added. This mixture was purged with nitrogen for 30minutes and transferred via a cannula to pre-nitrogen purged test tubes,which were sealed with rubber septa. The test-tubes were immersed in apre-heated water-bath at three different temperatures: 60, 70 and 80° C.The test tubes were removed from the water baths after various timeintervals. Polymerizations were allowed to proceed for a total of 9.5 h.After removal from the water bath, the samples were immediately cooledin ice water and stored in a freezer until analysis.

Temp Time Conversion M_(n) M_(n) CTA (° C) (min) (%)^(a) theory Expt^(b)M_(w)/M_(n) ^(b) TBP 60 580 1 400 7,400 1.67 TBP 70 580 25 10,000 30,6001.17 TBP 80 580 84 33,600 53,780 1.15 ^(a)As determined by ¹H NMRspectroscopy. ^(b)As determined by ASEC in 20% MeCN/80% 0.05 M Na₂SO₄employing RI and light scattering detectors.

Example 15 Preparation of Sodium2-(2-thiobenzoylsulfonyl-propionylamino)-ethanesulfonate Sodium2-(2-bromopropionylamino)-ethanesulfonate

25.6 g of taurine (204 mmol) and 16.38 g of NaOH (409 mmol) weredissolved in 20 ml of deionized water. 2-Bromopropionyl bromide (44 g,21.36 ml, 204 mmol) dissolved in 50 ml of dichloromethane was then addedto the solution drop wise at 0° C. over 30 minutes. During the addition,a large amount of solid was produced. The reaction flask was manuallyagitated to thoroughly mix the compounds until no more exotherm wasobserved with additional agitation. The reaction mixture was thenallowed to sit for 1 hour. The solid was filtered and washed with asmall amount of absolute ethanol and then ethyl ether and then dried invacuo. The compound can be used in this state or recrystallized frommethanol.

Sodium 2-(2-thiobenzoylsulfonylpropionylamino)-ethanesulfonate (STPE)

Freshly synthesized dithiobenzoic acid, sodium salt (9.12 g) dissolvedin 1 ml of water was combined with 8.5 g of crude sodium2-(2-bromopropionylamino)-ethanesulfonate dissolved in 6 ml of water ina 20 ml vial. Immediately upon mixing a precipitate started to formaccompanied by a strong exotherm. After 24 hours at room temperature,the solid was filtered and washed with a small amount of water. Theliquid portion was precipitated into acetone to yield a pink solid thatwas isolated by centrifugation. The precipitate was extracted withacetone until the liquid phase was a pale orange color. The precipitatewas dissolved in a minimum amount of water and recrystallized at 4° C.over several days. ¹H NMR δ=1.22, 1.45 (2d, 3H), 2.92 (d, 3H), 3.44 (d,3H), 4.35 (q, 1H), 7.29 (q, 2H), 7.44 (d, 1H), 7.76 (d, 2H). ¹³C NMR15.77, 35.55, 49.59, 50.08, 126.81 (CH), 128.82 (CH), 133.39 (CH),144.30 (C), 173.71 (C═O), 228.95 (C═S). Analysis for CHNS Calculated: C,40.55%, H, 3.97%, N, 3.91%, S, 27.07%. Found: C, 37.85%, H, 3.37%, N,3.58%, S, 25.26%.

Example 16 Polymerization of Acrylamide Using Sodium2-(2-thiobenzoylsulfonylpropionylamino)-ethanesulfonate (STPE)

2,2′-Azobis(2-methyl-N-(2-hydroxyethyl)-propionamide) (VA-086, Wako) wasutilized as the free radical initiator and STPE as the chain transferagent (CTA) with a CTA/I ratio of 1.15, an acrylamide concentration of2.0 M, a VA-086 concentration of 2.17×10⁻³ M, and a CTA concentration of2.50×10⁻³ M. The CTA/monomer ratio was chosen for a theoretical degreeof polymerization of 800 at 100% conversion. Buffer solutions (pH=5.0)for polymerization contained 0.272 M acetic acid and 0.728 M sodiumacetate. Solutions were placed in septa-sealed vials, purged for 30minutes with N₂, and heated to 70° C. with agitation. Aliquots wereremoved after 0, 2, 4, 8, 12, and 24 hours. A portion of each aliquotwas diluted and analyzed by aqueous size exclusion chromatography (ASEC)using an eluent of 20% acetonitrile/80% 0.05 M Na₂SO₄, Viscotek TSKViscogel column, Polymer Labs LC 1200 UV/vis, Wyatt Optilab DSPInterferometric refractometer, and Wyatt DAWN EOS multiangle laser lightscattering detectors. Conversions were determined by comparing the areaof the UV signal corresponding to monomer at t=0 to the area at t_(x).The dn/dc of polyacrylamide in the above eluent was previouslydetermined to be 0.160 at 25° C. Absolute molecular weights andpolydispersities were determined using the Wyatt ASTRA SEC/LS softwarepackage.

Chain extension of polyacrylamide was carried out as above but STPE wasreplaced by a polyacrylamide macro-CTA (molecular weight of 20300,polydispersity index (PDI) of 1.03) such that the CTA/monomer ratio andthe CTA/initiator was the same.

The polymerization of acrylamide in water at intermediate pH's producesresults typified by FIG. 7. In these polymerizations at pH=7 no polymeris observed for several hours during which the color is slowly bleachedfrom the polymerization solution. Only after all the color is gone,indicating complete loss of the dithioester moiety, is polymer observed.The very high molecular weights and broad polydispersities arecharacteristic of uncontrolled acrylamide polymerization. FIGS. 8A-8Cand Table 4, however, clearly demonstrate much better control of thepolymerization process simply by performing the polymerization in anacetic acid/sodium acetate buffer (pH=5.0). Under these conditions theevolution of molecular weight was clearly observed as peaks shifted toshorter retention times in ASEC (FIG. 8A). Further, the first order rateplot (FIG. 8B) and the plot of DP_(n) vs conversion (FIG. 8C) are bothlinear indicating controlled polymerization. Polydispersities weregenerally very low decreasing from 1.15 to between 1.04 and 1.06 atintermediate reaction times. At very long reaction times thepolydispersity increased to 1.26, remaining well below the theoreticallimit of 1.5 for conventional free radical polymerization.

TABLE 4 M_(n), Polymerization % M_(n) theoretical Time (h)Conversion^(a) (g/mol)^(a) (g/mol)^(b) PDI^(a) 0 0 — — — 2 3 5300 17101.15 4 9 9790 5120 1.05 8 11 13700 6260 1.04 12 18 18600 10200 1.06 2428 28900 15900 1.26 ^(a)determined by ASEC ^(b)calculated fromconversion

In order to further demonstrate the “livingness” of acrylamidepolymerization under these conditions, a polyacrylamide macro-CTA wasprepared (M_(n)=2.03×10⁴, PDI=1.03), isolated by dialysis andlyophilized to yield an orange powder. A polymerization solution wasthen prepared as before and this macro-CTA was used to extend thepolyacrylamide chain. FIG. 9 demonstrates that chain extension occurswith essentially quantitative blocking efficiency, indicating nearly allof the macro-CTA chain ends were active. A final 50/50 composition wastargeted for the first and extended segments (blocks). ASEC analysisindicated 2.03×10⁴ g mol⁻¹ and 1.8×10⁴ g mol⁻¹ for the respectivesegments, proving targeted molecular weights may be achieved.Interestingly, the molecular weights for all the polymers synthesizedwere substantially higher than the predicted theoretical molecularweights. This has also been observed for other neutral acrylamidomonomers polymerized in the presence of a dithioester compound.

While not being bound by theory, it is believed that the markeddifference in polymerization behavior of acrylamide under ambient andbuffered conditions is related to the extent of CTA degradationbyproducts generated during monomer hydrolysis.

Even a low percentage of acrylamide hydrolysis can produce enoughammonia to convert all dithioesters in solution to a thiol andthiobenzamide (at a molar ratio of monomer to CTA of 800 only 0.125% ofthe monomer needs to hydrolyze to quantitatively react with the CTA).Under low pH conditions, however, any ammonia produced via monomerhydrolysis would be effectively scavenged by the large excess of acid,thus greatly retarding nucleophilic attack on the dithioester. Examplesshown above eliminate an alternative possibility of direct CTAhydrolysis at neutral pH by demonstrating that RAFT proceeds well inwater for many monomers. Also, complete CTA hydrolysis at 70° C.requires days, in marked contrast to the hours observed in the case ofacrylamide.

In conclusion, conditions allowing excellent control of the RAFTpolymerization of acrylamide have been shown. The degree of control isillustrated in FIGS. 7 and 8A-C and Table 4 by the first order kineticplot, the GPC curves showing the evolution of molecular weight withconversion, the resulting DP vs. conversion relationship and the narrowPDI values. Nearly quantitative chain extension and the low PDI valuedemonstrate the maintenance of dithioester end groups duringpolymerization. It is apparent that the macro-CTA's prepared under theseconditions or those similar to the ones reported here will allowsynthesis of block copolymers and other complex polymer architecturescontaining polyacrylamide subunits.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

1. A dithioester or trithioester represented by the structural formula:

wherein: Z comprises an alkoxy group, a group represented by thestructural formula:

or one or more aromatic or heteroaromatic groups optionally substitutedby one or more hydrophilic functional groups wherein optionally there isan ether or alkylene linkage between the aromatic or heteroaromaticgroup and the dithioester moiety; and R comprises a group represented bythe structural formula:

wherein: Ar is an aromatic or heteroaromatic group; L is a bond, anC1-C20 azaalkylene group, or a C1-C20 straight-chained or branchedalkylene group; R₁ and R₂ are each independently hydrogen, a C1-C10alkyl group, or a cyano group; R₃ and R₄ are each independently hydrogenor a C1-C10 alkyl group when Y is N or C, and are each lone electronpairs when Y is O; R₅ is a bond or a branched or straight-chained C1-C10alkylene group; R₆ is hydrogen or a C1-C10 alkyl group; W is selectedfrom the group consisting of —H, —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂,—NR′H, —NR′₃ ⁺X⁻, PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)R′, —(—CH₂CH₂O—)_(x)R′,—CONH₂, —CONHR′, —CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,—NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺,—N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺, —SCN, naphthyl, and dansyl; M⁺ is ammonia, anammonium ion, an alkali metal ion, an alkaline earth metal ion, orhydronium; R′ is independently hydrogen or an alkyl group; x is aninteger from 1 to about 20; X⁻ is a halide, sulfate, phosphate,carboxylate, or sulfonate; and Y is selected from the group consistingof N, O, and C.
 2. The dithioester or trithioester of claim 1, wherein Ris substituted by one or more hydrophilic functional groups selectedfrom the group consisting of —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺, —NH₂, —NR′₂,—NR′H, —NR′₃ ⁺X⁻, PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)H, —CONH₂, —CONHR′,—CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺, —NR′(CH₂)_(x)SO₃⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)SO₃⁻M⁺, or a combination thereof.
 3. The dithioester or trithioester ofclaim 1, wherein Z is substituted by one or more hydrophilic functionalgroups selected from the group consisting of —SO₃ ⁻M⁺, —COOH, —COO⁻M⁺,—NH₂, —NR′₂, —NR′H, —NR′₃ ⁺X⁻, PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)H, —CONH₂,—CONHR′, —CONR′₂, —NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,—NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺,—N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺, or a combination thereof.
 4. The dithioester ortrithioester of claim 1, wherein R₁ and R₂ are each independentlyhydrogen or a methyl group.
 5. The dithioester or trithioester of claim4, wherein Z comprises a phenyl, benzyl, pyrrole, indole, isoindole, orethoxy group.
 6. The dithioester or trithioester of claim 5, wherein Ris represented by a structural formula selected from the groupconsisting of:

m and n are each integers from 1 to about 10; R₇, R₈, R₉, R₁₀, and R₁₁are each independently hydrogen or a C1-10 alkyl group; L, M⁺, R′, W,X⁻, x, and Y are as defined above; and V is selected from the groupconsisting of C and N.
 7. The dithioester or trithioester of claim 6,wherein R₇ and R₈ are each independently hydrogen or a methyl group. 8.The dithioester or trithioester of claim 5, wherein Z is represented bya structural formula selected the group consisting of:


9. The dithioester or trithioester of claim 5, wherein R is:

wherein x is an integer from 1 to about 20; and X⁻ is a halide, sulfate,phosphate, carboxylate, or sulfonate.
 10. The dithioester of claim 1selected from the group consisting of:

wherein R comprises a group represented by the structural formula:

wherein: Ar is an aromatic or heteroaromatic group; L is a bond, anC1-C20 azaalkylene group, or a C1-C20 straight-chained or branchedalkylene group; R₁ and R₂ are each independently hydrogen, a C1-C10alkyl group, or a cyano group; R₃ and R₄ are each independently hydrogenor a C1-C10 alkyl group when Y is N or C, and are each lone electronpairs when Y is O; R₅ is a bond or a branched or straight-chained C1-C10alkylene group; R₆ is hydrogen or a C1-C10 alkyl group; W is selectedfrom the group consisting of —H, —SO₃ ⁻M⁺, —COOH,  COO⁻M⁺, —NH₂, —NR′₂,—NR′H, —NR′₃ ⁺X⁻, PO₄ ⁻M⁺, —OH, —(—OCH₂CH₂—)_(x)R′, —(—CH₂CH₂O—)_(x)R′,—CONH₂, —CONHR′, —CONR′₂,  NR′(CH₂)_(x)COO⁻M⁺, —NR′(CH₂)_(x)OPO₃ ⁻M⁺,—NR′(CH₂)_(x)SO₃ ⁻M⁺, —N⁺R′₂(CH₂)_(x)COO⁻M⁺, —N⁺R′₂(CH₂)_(x)OPO₃ ⁻M⁺,—N⁺R′₂(CH₂)_(x)SO₃ ⁻M⁺,  SCN, naphthyl, and dansyl; M⁺ is ammonia, anammonium ion, an alkali metal ion, an alkaline earth metal ion, orhydronium; R′ is independently hydrogen or an alkyl group; x is aninteger from 1 to about 20; X⁻ is a halide, sulfate, phosphate,carboxylate, or sulfonate; and Y is selected from the group consistingof N, O, and C.
 11. The dithioester of claim 1 selected from the groupconsisting of:

wherein: M⁺ is ammonia, an ammonium ion, an alkali metal ion, analkaline earth metal ion, or hydronium.